Clinical and operational impact of rapid point-of-care SARS-CoV-2 detection in an emergency department.

STUDY OBJECTIVE: Rapid point-of-care (POC) SARS-CoV-2 detection with Abbott ID NOW™ COVID-19 test has been implemented in our Emergency Department (ED) for several months. We aimed to evaluate the operational impact and potential benefits of this innovative clinical pathway. METHODS: We conducted a prospective, descriptive, interventional, non-randomized study, before-after trial with the comparison of patient cohorts from two consecutive periods of seven weeks (observational pre-POC period vs interventional POC period). RESULTS: In 2020, throughout weeks 37 to 50, 3333 patients were assessed for eligibility and among them 331 (9.9%) were positive for SARS-CoV-2 infections. Among the included patients, 136 (9.2%) were positive for SARS-CoV-2 infection in the pre-POC period and 195 (10.5%) in the POC period. Among positive patients for SARS-CoV-2 related infection in-hospital mortality rate was similar between the two groups but the hospitalization rate was higher in the POC group (81.6% vs. 65.4%; p < 0.001). More patients in the POC period were able to leave the ED within 6 h. We examined rates of antibiotic, anticoagulant, and corticosteroid prescriptions among patients tested for SARS-CoV-2 in the ED. Only the rate of prescribed anticoagulants was found to be higher in the POC period (40% vs. 24.2%; p < 0.003). CONCLUSION: We demonstrated that COVID-19 point-of-care testing speeds up clinical decision-making, improving use of recommended treatments for COVID-19, such as anticoagulants. Moreover, it improves the boarding time and significantly shortened the length of stay in the ED for patients requiring outpatient care.

Clinical impact of rapid susceptibility testing on Mueller-Hinton Rapid-SIR directly from urine specimens.

Urinary tract infection diagnosis and management generally involves a 48-h microbiological delay to obtain the antibiotic susceptibility test (AST) results. In the context of multidrug resistance, reducing the time to obtain AST results is an essential factor, allowing for more timely appropriate treatment. We conducted a single-centre prospective study on urinary samples meeting two criteria: significant leukocyturia > 50/mm3 and exclusive presence of Gram-negative bacilli on direct examination. AST were performed by direct inoculation on Mueller-Hinton Rapid-SIR (MHR-SIR) agar. We evaluated the time to antibiotic adaptation by the antimicrobial stewardship team according to rapid AST results. Patients were subsequently excluded from the study if asymptomatic bacteria were confirmed, or in the absence of clinical data. Seventy patients were included. Mean age of patients was 68.8 years (± 21.3). Empirical antibiotic treatment were mainly based on third generation cephalosporins (n = 33), fluoroquinolones (n = 15), beta-lactamin/beta-lactamase inhibitors (n = 7), fosfomycin and nitrofurantoin (n = 5, each). The average time to obtain results was 7.2 h (± 1.6 h). Adaptation of therapy following MHR-SIR was performed for 29 patients (41%) with early switch to oral antibiotics, de-escalation or escalation in respectively 72.3%, 30%, and 11% of cases. Time saving of MHR-SIR compared with the standard technique was 42.6 (± 16.7) h. This study showed that rapid antibiotic susceptibility test results, using MHR-SIR method directly from urine, can be obtained 40 h earlier than conventional AST. The study also demonstrated significant clinical impact on the selection and reduction of the antibiotic therapy spectrum.

Impact of a multiplex PCR assay (FilmArray®) on the management of patients with suspected central nervous system infections.

Microbiological diagnosis of central nervous system (CNS) infections is challenging due to limited access to CNS samples, overlap between meningitis and encephalitis, and the multiplicity of pathogens potentially involved. We aimed to estimate the impact of a commercial multiplex PCR assay (FilmArray® meningitis/encephalitis) on the management of patients with suspicion of meningitis or encephalitis, in terms of time to diagnosis, antimicrobial agents use, duration of hospitalization, and costs. This prospective observational study was conducted at Saint Joseph Hospital (Paris, France) from December 2016 to December 2017. All CSF samples sent to the microbiology laboratory for suspicion of meningitis and/or encephalitis, with CSF cells count > 5 cells/µL, were tested by meningitis/encephalitis multiplex PCR assay. One hundred thirty patients were included. The multiplex PCR assay was positive in 33 patients (25%). Main pathogens found were Enterovirus (n = 12), Varicella-Zoster virus (n = 7), Herpes simplex virus-2 (n = 6), and Listeria monocytogenes (n = 3) as main pathogens. The multiplex PCR assay reduced time to microbiological diagnosis by 3.3 ± 1.6 days and allowed an earlier discontinuation of empirical anti-infective drugs in 42 patients (32%) and an earlier hospital discharge in 23 patients (18%), with an estimated saving of 82 hospital days overall, and a management cost reduction of 26,242 € (201 €/patient). The systematic use of the FilmArray® meningitis/encephalitis multiplex PCR assay may allow earlier diagnosis, earlier discontinuation of empirical treatment, reduced duration of stay, and costs reduction.

Clinical impact of rapid susceptibility testing on MHR-SIR directly from blood cultures.

BACKGROUND: In a previous study, we demonstrated that rapid antibiotic susceptibility tests (ASTs) can be performed directly on blood culture samples tested on Mueller-Hinton Rapid agar (MHR-SIR) with a time delay of 6-8 h. OBJECTIVES: Using this rapid disc diffusion method, we analysed the clinical impact associated with rapid reporting of results in our hospital setting. METHODS: All patients with bloodstream infections (BSIs) related to Enterobacteriaceae or Staphylococcus aureus were prospectively included in the study. The rapid ASTs were performed by incubation of positive blood cultures on MHR-SIR for 6-8 h by direct inoculation according to BSAC recommendations. RESULTS: One hundred and sixty-seven patients with BSIs were included as MHR-guided adaptation therapy cases. Eighty percent had Enterobacteriaceae-related BSIs, of which 12 (9%) were ESBL producers and 20% were S. aureus-related BSIs. A urinary or intra-abdominal infection was observed in 44.3% and 19.8%, respectively, of Enterobacteriaceae-related infections. The most frequent sources of infections for S. aureus BSIs were cutaneous and endovascular, in 43% and 23% of cases, respectively. Forty-four percent of the patients benefited from therapeutic modification according to the results of the MHR-SIR AST. Thus, empirical antibiotic therapy was modified by using antibiotic therapy that had too wide a spectrum or was unsuitable in 26% and 18% of cases, respectively. Compared with the 24 h required for the reference method, the median length of time to provision of susceptibility test results by MHR-SIR was 7 h. CONCLUSIONS: This study showed a significant time saving (17 h) on the appropriateness of antibiotic prescription and demonstrated a significant impact regarding the choice and reduction of the spectrum of antibiotic therapy.

Performance of rapid antimicrobial susceptibility testing by disk diffusion on MHR-SIR agar directly on urine specimens.

The standard method for the diagnosis of urinary tract infections is urine culture that requires 18-48 h for the identification of the bacteria and an additional 24 h until the results of antimicrobial susceptibility testing (AST) are available. We evaluated here a rapid AST method by disc diffusion performed directly on urine samples with a delay of 8 h. A total of 245 urine samples with monobacterial Gram negative observed on microscopy were tested in parallel by two AST methods. Rapid AST method was performed directly on urine samples using Rapid Mueller-Hinton (MHR-SIR) with 8-h incubation before reading and standard method was performed as usual. We compared the categorical agreement and the correlation between the diameters obtained by standard method and by MHR-SIR directly on urine samples. Over the 5285 tested combinations, we observed 5172 (97.9%) categorical agreement, 82 (1.5%) minor errors, 17 (0.3%) major errors, and 14 (0.3%) very major errors. Our results showed an excellent categorical agreement and correlations between diameters for MHR-SIR and standard methods. MHR-SIR performed directly on urine samples with monomicrobial Enterobacteriacae can predict the result of overall AST profile in 8 h with reliable results. The main advantage of MHR-SIR is that it offers the possibility of obtaining results 40 h earlier than conventional AST. The cost is estimated for less than 6 USD for 16 antibiotics, chosen by the microbiologist.

Pharmacokinetic variability of clindamycin and influence of rifampicin on clindamycin concentration in patients with bone and joint infections.

PURPOSE: Clindamycin, a lincosamide antibiotic with a good penetration into bone, is widely used for treating bone and joint infections by Gram-positive pathogens. To be active against Staphylococcus spp, its concentration at the infection site, C, must be higher than 2× the minimal inhibitory concentration (MIC). The aims of the work were to study the determinants of plasma clindamycin trough concentration, C min, especially the effect of co-treatment with rifampicin, and the consequences on clinical outcome. METHODS: An observational study was performed, involving patients hospitalized for a bone and joint infection who received clindamycin as part of their antibiotic treatment. Target C min was 1.7 mg/L, to reach the desired bone concentration/MIC >2, assuming a 30% diffusion into bone and MIC = 2.5 mg/L. RESULTS: Sixty one patients (mean age: 56.8 years, 57.4% male) were included between 2007 and 2011. 72.1% underwent a surgery on a foreign material, and 91.1% were infected by at least a Gram-positive micro-organism. Median C min value was 1.39 mg/L, with 58% of the values below the threshold value of 1.7 mg/L. Median C min was significantly lower for patients taking rifampicin (0.46 vs 1.52 mg/L, p = 0.034). No patient with rifampicin co-administration reached the target concentration (maximal C min: 0.85 mg/L). After a median follow-up of 17 months (1.5-38 months), 4 patients relapsed, 2 died and 47 (88.7% of the patients with known outcome) were cured, independently of association with rifampicin. CONCLUSIONS: This study shows the high inter-variability of plasma clindamycin concentration and confirms that co-treatment with rifampicin significantly decreases clindamycin trough concentrations.

[Feedback on the detection of SARS-CoV-2 by the point-of-care testing]. / Retour d'expérience de la détection du SARS-CoV-2 par biologie moléculaire délocalisée.

In order to improve the detection and rapid diagnosis of the SARS-CoV-2 coronavirus, we evaluated the ID NOW™ COVID-19 isothermal gene amplification technique in parallel with the real-time PCR technique (Diasorin) routinely used in the laboratory during a prospective study in the 2020 season. As this technique showed satisfactory sensitivity and specificity of 98% and 97.5% respectively, we then proposed to implement the detection of SARS-CoV-2 coronavirus in the emergency department and maternity as a point-of-care test (POCT) for the 2020-2021 season and to evaluate its clinical and organizational impact. This article summarizes the results obtained and highlights the advantages and limitations of this strategy implemented in the emergency department, particularly in terms of time spent in the department, hospitalization rates, anticoagulant treatment and early isolation of patients, as well as the organizational impact on the maternity unit. Based on this experience, we report on the regulatory constraints that apply when setting up a POCT and the steps required to validate the accreditation in accordance with standard NF EN ISO 22870.

The Coris BioConcept COVID 19 Ag Respi-Strip, a field experience feedback.

This communication described how the Coris BioConcept COVID-19 Ag Respi-Strip test (Coris-Ag) was implemented in the workflow of our clinical microbiology laboratory for COVID-19 diagnosis. The diagnostic performance statistics (sensitivity, specificity) of the Coris-Ag were evaluated against a gold standard, the RealStar SARS-CoV-2 RT-PCR kit 1.0. Additionally, the effect of reading the Coris-Ag results at 30 min was compared to reading at 15 min. The Coris-Ag was performed on a total of 294 patients during two periods; 158 patients were tested during period 1 at the peak of the pandemic (April 6th to April 10th 2020) which returned a positivity rate of 17.1 %, and 136 patients during period 2 (April 12th to April 16th 2020) which returned a positivity rate of 11 %. Compared to the RT-PCR, the 15-minute Coris-Ag readings resulted in a sensitivity of 59.3 % with a 100 % specificity for the period 1 patients (n = 158) while the sensitivity decreased to 20 % for the period 2 patients (n = 136). The overall sensitivity was 38.1 % for both periods (n = 294). The corresponding 30-minute readings produced a 7 % increase in sensitivity with a specificity of 100 % (n = 294). The sensitivity of the strip test (15-min reading) for high viral loads (Ct <25) was 84.6 %.

No significant difference between ceftriaxone and cefotaxime in the emergence of antibiotic resistance in the gut microbiota of hospitalized patients: A pilot study.

BACKGROUND: Ceftriaxone and cefotaxime share a similar antibacterial spectrum and similar indications but have different pharmacokinetic characteristics. Ceftriaxone is administered once daily and 40% of its clearance is by biliary elimination, whereas cefotaxime requires three administrations per day and shows less than 10% biliary elimination. The high biliary elimination of ceftriaxone suggests a greater impact of this antibiotic on the gut microbiota than cefotaxime. The objective of this study was to compare the impact of ceftriaxone and cefotaxime on the gut microbiota. METHODS: A prospective clinical trial was performed that included 55 patients treated with intravenous ceftriaxone (1 g/24 h) or cefotaxime (1 g/8 h) for at least 3 days. Three fresh stool samples were collected from each patient (days 0, 3, and 7 or at the end of intravenous treatment) to assess the emergence of third-generation cephalosporin (3GC)-resistant Enterobacteriaceae, carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa, toxigenic Clostridioides difficile, and vancomycin-resistant enterococci. RESULTS: The emergence of 3GC-resistant gram-negative enteric bacilli (Enterobacteriaceae) (5.9% vs 4.7%, p > 0.99), Enterococcus spp, and non-commensal microorganisms did not differ significantly between the groups. Both antibiotics reduced the counts of total gram-negative enteric bacilli and decreased the cultivable diversity of the microbiota, but the differences between the groups were not significant. CONCLUSION: No significant difference was observed between ceftriaxone and cefotaxime in terms of the emergence of resistance.

Evaluation of the Unyvero i60 ITI® multiplex PCR for infected chronic leg ulcers diagnosis.

OBJECTIVES: Unyvero i60 ITI multiplex PCR (mPCR) may identify a large panel of bacteria and antibiotic resistance genes. In this study, we compared results obtained by mPCR to standard bacteriology in chronic leg ulcer (CLU) infections. METHODS: A prospective study, part of the interventional-blinded randomized study "ulcerinfecte" (NCT02889926), was conducted at Saint Joseph Hospital in Paris. Fifty patients with a suspicion of infected CLU were included between February 2017 and September 2018. Conventional bacteriology and mPCR were performed simultaneously on deep skin biopsies. RESULTS: Staphylococcus aureus and Pseudomonas aeruginosa were the most detected pathogens. Regarding the global sensitivity, mPCR is not overcome to the standard culture. Anaerobes and slow growing bacteria were detected with a higher sensitivity rate by mPCR than standard culture. CONCLUSION: Unyvero i60 ITI multiplex PCR detected rapidly pathogenic bacteria in infected CLU especially anaerobes and slow growing bacteria and was particularly effective for patients previously treated with antibiotics.

Prospective evaluation of rapid antimicrobial susceptibility testing by disk diffusion on Mueller-Hinton rapid-SIR directly on blood cultures.

BACKGROUND: With the worldwide spread of antibiotic resistance, delivering antibiotic susceptibility test (AST) results in a timely manner represents a major challenge. In cases of sepsis, rapid AST may facilitate early optimization of empiric antibiotic therapy. Disc diffusion is a well-standardized AST method, however 16 to 24 h are required to achieve an overall AST profile according to antimicrobial societies. METHODS: In this prospective pilot study, we evaluated the performance of Mueller-Hinton-Rapid-SIR (MHR-SIR) agar after 6-8 h of incubation in comparison with standard MH agar after 16 h of incubation directly on positive blood cultures caused by Enterobacteriaceae and Staphylococcus aureus from routine clinical microbiology. A total of 133 positive blood samples including 110 Enterobacteriaceae (83%) and 23 Staphylococcus aureus (17%) were tested in parallel by two direct AST methods, each using EUCAST breakpoints. For each combination bacterium and antibiotic, we compared the categorical agreement and the correlation between the diameters obtained by MHR-SIR and by standard MH. RESULTS: Our results showed 97.7% categorical agreement for Enterobacteriaceae, with 1.4% minor errors, 0.4% major errors and 0.5% very major errors. For S. aureus, we observed 97.8% categorical agreement, 1.9% minor errors, 0.3% major errors and no very major errors. CONCLUSION: Our results showed excellent categorical agreement and correlations between diameters for MHR-SIR and standard MH methods. MHRSIR can predict the result of overall AST profile within 6-8 h with reliable results. AST is obtained on the same day the blood culture becomes positive, with a very moderate cost.

The effects of antibiotic cycling and mixing on antibiotic resistance in intensive care units: a cluster-randomised crossover trial.

BACKGROUND: Whether antibiotic rotation strategies reduce prevalence of antibiotic-resistant, Gram-negative bacteria in intensive care units (ICUs) has not been accurately established. We aimed to assess whether cycling of antibiotics compared with a mixing strategy (changing antibiotic to an alternative class for each consecutive patient) would reduce the prevalence of antibiotic-resistant, Gram-negative bacteria in European intensive care units (ICUs). METHODS: In a cluster-randomised crossover study, we randomly assigned ICUs to use one of three antibiotic groups (third-generation or fourth-generation cephalosporins, piperacillin-tazobactam, and carbapenems) as preferred empirical treatment during 6-week periods (cycling) or to change preference after every consecutively treated patient (mixing). Computer-based randomisation of intervention and rotated antibiotic sequence was done centrally. Cycling or mixing was applied for 9 months; then, following a washout period, the alternative strategy was implemented. We defined antibiotic-resistant, Gram-negative bacteria as Enterobacteriaceae with extended-spectrum ß-lactamase production or piperacillin-tazobactam resistance, and Acinetobacter spp and Pseudomonas aeruginosa with piperacillin-tazobactam or carbapenem resistance. Data were collected for all admissions during the study. The primary endpoint was average, unit-wide, monthly point prevalence of antibiotic-resistant, Gram-negative bacteria in respiratory and perineal swabs with adjustment for potential confounders. This trial is registered with ClinicalTrials.gov, number NCT01293071. FINDINGS: Eight ICUs (from Belgium, France, Germany, Portugal, and Slovenia) were randomly assigned and patients enrolled from June 27, 2011, to Feb 16, 2014. 4069 patients were admitted during the cycling periods in total and 4707 were admitted during the mixing periods. Of these, 745 patients during cycling and 853 patients during mixing were present during the monthly point-prevalence surveys, and were included in the main analysis. Mean prevalence of the composite primary endpoint was 23% (168/745) during cycling and 22% (184/853) during mixing (p=0·64), yielding an adjusted incidence rate ratio during mixing of 1·039 (95% CI 0·837-1·291; p=0·73). There was no difference in all-cause in-ICU mortality between intervention periods. INTERPRETATION: Antibiotic cycling does not reduce the prevalence of carriage of antibiotic-resistant, Gram-negative bacteria in patients admitted to the ICU. FUNDING: European Union Seventh Framework Programme.

Septic arthritis of the hip with Propionibacterium avidum bacteremia after intraarticular treatment for hip osteoarthritis.

Propionibacterium avidum is a Gram-positive, nonsporulating, facultative anaerobe that has a low level of virulence and is rarely pathogenic. This ubiquitous inhabitant of the sebaceous glands and hair follicles can cause acne vulgaris. Very rarely, P. avidum causes systemic infections after invasive procedures, most notably in immunocompromised patients. Two cases of sacroiliitis due to P. avidum have been reported. We report a case of P. avidum arthritis of the hip with severe sepsis that developed in a 78-year-old woman after intraarticular glucocorticoid treatment for hip osteoarthritis. We are unaware of previous reports of P. avidum hip arthritis.

Typhoid fever due to a Salmonella typhi strain of reduced susceptibility to fluoroquinolones.

OBJECTIVE: To report a case of typhoid fever contracted in Portugal in 1994 due to a Salmonella typhi isolate which had reduced susceptibility to fluoroquinolone (MIC 1 mg/L of ciprofloxacin) and high level resistance to nalidixic acid (MIC greater-than-or-equal 56 mg/L). METHODS: Molecular studies of reduced susceptibility to fluoroquinolones comprised complementation tests with a wild-type allele and sequencing directly from PCR products of the gyrA gene. RESULTS: Complementation tests and DNA sequencing showed that a mutation occurred in the gyrA gene of this clinical isolate, resulting in a substitution of phenylalanine for serine at position 83 of GyrA. CONCLUSIONS: Because quinolones may be regarded as a treatment of choice in typhoid fever, it seems important now to recommend cautious use of these drugs as first-line therapy and possibly use of nalidixic acid resistance as a marker for detection of 'first-step' resistance to fluoroquinolones in S. typhi.